FDA’s New Inspection Protocol Begins to Have Impact

The FDA’s New Inspection Protocol Project (NIPP) is expected to increase the likelihood of a drug manufacturing facility undergoing a pre-approval inspection from the current average of 30 percent to a target of 50 percent.

“As a pharma company if you’re going to submit a new drug, instead of a 30 percent chance of getting a pre-approval inspection, it’s now 50/50 as the FDA transitions to largely pre-approval and post-market surveillance inspections,” said John Avellanet, Managing Director & Principal of Cerulean Associates LLC. “So now instead of threatening your management and saying we might get an inspection, it’s more like we’re going to get inspected. No more are you going to have a situation where a company has submitted a drug for approval and the agency pops by six or nine months later and finds out company personnel can’t even spell the drug, which is something you can see today.”

In addition to pre-market inspections, the protocol will help with inspection uniformity, as different investigators may look at different aspects of facility operations. A drug company may receive a warning letter from an investigator who looks at big picture factors, such as sterility methods and cleanliness, or from one who puts an emphasis on data integrity and aggressively looking for fraud.

That has sometimes created a rift between investigators and the industry in the past, but now investigators will be directed at what to look for, which will give facilities and companies a better idea of what to prepare for.

“Another issue this solves is that companies never know based upon who’s conducting the inspection whether the investigator will understand realities and go along with the shades of grey or if they’re going to be nitpicky and issue a FDA-483 observation because someone forgot to sign a training letter from seven years ago,” Avellanet said. “The industry has just about had it with that type of inspection. One goal of the NIPP is also to eliminate as much of this annoyance stuff as possible.”

Now, inspections will put more emphasis on the documented quality controls and proof a firm has in place, the actual behaviors in the day-to-day operations, and further transition agency inspections to a risk-based inspection plan. The project also aims to standardize the FDA’s inspection process world-wide and to allow for increased reliance on inspections by sister agencies such as Health Canada and the European Medicines Agency (EMA).

The data that the FDA will rely on “is pretty intense and incorporates information from the original product submissions for market approval, subsequent submissions, and adverse events reported by the firm versus reported directly to FDA,” Avellanet said. “It will also use data from previous inspection results from both FDA and sister regulatory agencies.”

The protocol is expected to be fully operational by the end of 2018. The next two years will be used to get FDA investigators trained and acclimated to the new standards and also to “provide time for feedback from investigators as they slowly go out and conduct these inspections — what’s working, what isn’t and what could be better — and then incorporate that to continuously improve the program.” Avellanet said.

Although Avellanet believes the new protocol is an improvement to handling inspections and keeping the public safe, it may be some time before the industry can see how much better it will be.

“They’ll get all the investigators trained within the next couple of years and everybody will be implementing it and using it, but the real proof in the pudding of ‘is this working’ really won’t be available until 2020.”

Adapted for the web from the original October 2016 publication in FDAnews’ Drug Industry Daily.

Client Success Story

Cerulean was a true partner. John was instrumental in guiding the development of a FDA compliant quality system from ground zero in record time. This was accomplished in an environment of limited resources and rapidly changing processes. Through it all, he was a delight to work with and always brought more to the table than we were expecting.